MO272CLINICOPATHOLOGICAL CORRELATION OF APRIL AND BAFF IN IG A NEPHROPATHY- A SINGLE CENTER LONGITUDINAL OBSERVATIONAL STUDY

Abstract

Abstract Background and Aims Aberrantly glycosylated IgA1 molecules are important in the pathogenesis of IgA nephropathy. A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are cytokines involved in immunoglobulin class switching and production of galactose deficient IgA1(Gd IgA1). We aimed to study the association of serum levels of APRIL and BAFF with the clinical severity and pathological grading of IgA nephropathy (IgAN) and to assess the strength of the association by studying the clinicopathological correlation. Method The research study was conducted as a single-center longitudinal observational study. The study subjects were recruited based on the pathological diagnosis of primary IgA nephropathy. The plasma levels of APRIL, BAFF and Gd IgA1 were estimated using enzyme-linked immunosorbent assay (ELISA). All the study subjects were followed up for one year to study the renal outcome. Results In our study group of thirty-eight patients, the median estimated glomerular filtration rate(eGFR) was 33.9(15.9,79.4) ml/minute/1.73m2. The median levels of the cytokines APRIL and BAFF were 170.81(82.45, 550.61) ng/L and 6.66(3.39,16.33) ng/ml respectively. The baseline characteristics of the study group is given in table 1. APRIL levels had significant positive correlation with Gd IgA1 levels (correlation coefficient 0.556, p=0.003) in patients with IgAN. We also observed that patients with elevated APRIL levels had elevated BAFF levels also (correlation coefficient 0.657, p <0.001). Patients who had crescents, mesangial hypercellularity and endocapillary proliferation in biopsy had elevated APRIL and BAFF levels whereas patients with segmental sclerosis and tubular atrophy had low levels of APRIL(Table 2). However, the levels of APRIL and BAFF did not show any significant correlation with eGFR and proteinuria at time of presentation. At the end of one year, 12(31.5%) patients reached end stage renal disease (ESRD) and these patients had lower levels of APRIL, BAFF, and Gd IgA1. It was also seen that eighty-three percent of those who reached ESRD had chronic changes in biopsy like tubular atrophy and interstitial fibrosis(p=0.05). Hence the severity of tubulointerstitial fibrosis in histology correlated well with progression to end stage renal disease as seen in most glomerular diseases. But we did not find any association between APRIL, BAFF, and Gd IgA1 levels and the decline in eGFR over one year. Conclusion We conclude that levels of APRIL and BAFF are associated with elevated levels of Gd IgA1 in patients with IgAN and had a significant association with proliferative lesions in renal biopsy. But these cytokines levels did not have any association with the eGFR at time of presentation nor decline in eGFR over one year.